PB2156: ANALYSIS OF POSSIBLE CLONAL ORIGIN OF LARGE B-CELL DIFFUSED LYMPHOMAS ARISING IN PATIENTS WITH PRE-EXISTING HODGKIN’S LYMPHOMA
Authors: P. Masciopinto, E. Bellitti, G. Opinto, E. Arcuti, L. Mastracci, S. Ciavarella, G. Cazzato, A. Guarini, E. Maiorano, P. Musto, G. Ingravallo, F. Gaudio
Journal: HemaSphere (2022)

Background: Lymphomas are a variegated group of lymphoproliferative diseases featuring differences in cellular origin, biological development, clinical signs and symptoms and outcome. In fact, they derive from lymphocytes at various stages of development, and the characteristics of the specific subtype of lymphoma mirror those of the cell from which they originated. However, in some cases, a synchronic or metachronic onset of two different lymphomas in the same patient is possible. Aims: This retrospective study was focused on 269 patients with newly diagnosed classic Hodgkin lymphomas treated at Bari University Hospital (Italy) between 2007 and 2020, with the aim of identifying patients who developed DLBCL and verifying a possible common origin. Methods: All patients were clinically staged according to the Ann-Arbor system, recording the medical history, complete physical examination, blood counts, biochemical profile, chest X-ray films, PET/CT total body, computed tomography of the chest, abdomen and pelvis, unilateral bone marrow biopsy. Median age at diagnosis was 35 years (range 15-83), 90 pts (33%) had advanced stage (III-IV), 110 (41%) bulky disease, 123 (46%) presented B symptoms, and 71 (26%) extranodal disease. In addition to the routine pathological examination, PD-L1 was assayed as a critical marker to differentiate Primary mediastinal large B-cell lymphoma from other entities. CD3 and CD5 expression, as well as that of PD-L1, was evaluated to identify some characteristics of the tumor microenvironment (TME). Cell-of-Origin (COO) was analyzed according to the Hans algorithm and with gene expression profile. With the Nanostring Lymphoma Subtype (LST) Assay we evaluated the expression profile of 20 genes within the LST signature, 15 target genes and 5 reference genes. Results: Over the study period, 269 patients were diagnosed with cHL; in 4 patients (1.5%), DLBCL developed after a median time of 53 months. The mean age at presentation with cHL was 28 years (range 18-76 years), and the mean age when DLBCL was diagnosed was 35 years (range 21-79). Morphological review of histological slides, as well as immunohistochemical evaluation, confirmed the previous diagnosis. All cHL cases were positive to PD-L1 against a non-neoplastic inflammatory background, while only two patients with DLBCL revealed positivity in a high percentage of neoplastic cells Using Hans’s algorithm, all DLBCL cases showed a non-GBC subtype. None of the DLBCLs showed EBV infection detected by EBER. The gene expression profile evaluated by the Nanostring Lymphoma Subtype Assay revealed two cases of the GCB molecular subtype, while the others were not classified. Regarding the T cell background, only two cases showed a diffuse and prominent CD3+/CD5+ population, while the other cases showed sporadic T cell infiltration. Summary/Conclusion: The origin of the second neoplastic cell, in patients with DLBCL with a previous history of cHL, remains controversial, although the different immunophenotypic characteristics suggest that it may mainly arise de novo in a subject with a possible individual predisposition to develop lymphoid neoplasms. Large studies are necessary to verify the distinct roles of environmental factors, individual predispositions and constitutional or immune dysfunction consequent to previous treatment.